20 replies to this topic

[Spinlock]

A couple of conflicting studies have come out on L Carnintine in the past few months with regards to cardiovascular health. The first article claiming it's dangerous changes tone 1/2 way through and suggests that the findings are inconclusive.


http://www.health.ha...se-201304176083

According to this work, published online in the journal Nature Medicine, eating red meat delivers L-Carnitine to bacteria that live in the human gut. These bacteria digest L-carnitine and turn it into a compound called trimethylamine-N-oxide (TMAO). In studies in mice, TMAO has been shown to cause atherosclerosis, the disease process that leads to cholesterol-clogged arteries. We know that clogged coronary arteries can lead to heart attacks.

http://www.scienceda...30412132321.htm

L-carnitine significantly improves cardiac health in patients after a heart attack, say a multicenter team of investigators in a study.

I take this supplement and so do a lot of others so I would like to hear peoples thoughts on it.

[niner]

Regarding the apparent conflict between those two quotes:

Chronic carnitine in a healthy person might lead to atherosclerosis over a long period of time.

Carnitine is helpful *after a heart attack*.

These two statements aren't contradictory. The same carnitine that is helping the compromised heart could also be slowly worsening the artery dysfunction that led to the heart attack. Carnitine has both desirable and undesirable effects. The desirable effects happen in the short term, while the bad effects take years to fully manifest.

I've dropped ALCAR and I don't seem to miss it. I initially liked it for the effect it had on my perceived energy level at the gym, but c60-oo seems to be handling that just fine now.

[Luddist]

Isn't it probable the TMAO-induced atherosclerosis, like most things, is dose dependent? Were the mice fed proportional doses of carnitine or were they directly given TMAO at some dose, possibly a much higher dose than a human would ever see from eating red meat or even supplementing carnitine? These are some big and obvious questions that should be answered before publishing alarmist articles.

[Kevnzworld]

I seem to remember that the conversion of Carnitine to TMAO was dependent on a particular strain of gut bacteria, that may not necessarily translate to most healthy humans.

[YOLF]

IIRC the bacteria lives in meat, if you eat it, you have it. I would think that because gut bacteria proliferate quickly, feeding them would increase their numbers rapidly and lead to large increases in TMAO production. Though I'm not aware of any baseline info. The study came from Harvard, I would expect them to be pretty good vetters of things.

[Andey]

Regarding the apparent conflict between those two quotes:

Chronic carnitine in a healthy person might lead to atherosclerosis over a long period of time.

Carnitine is helpful *after a heart attack*.

These two statements aren't contradictory. The same carnitine that is helping the compromised heart could also be slowly worsening the artery dysfunction that led to the heart attack. Carnitine has both desirable and undesirable effects. The desirable effects happen in the short term, while the bad effects take years to fully manifest.

I've dropped ALCAR and I don't seem to miss it. I initially liked it for the effect it had on my perceived energy level at the gym, but c60-oo seems to be handling that just fine now.

Sometimes you write things that contradicts with public sense about some supplements. Based on the fact that you are one of the most informed members of community and make an aware decisions it would be very interesting to see your regimen. )

[nowayout]

There could be a large difference between carnitine in meat and in supplements. Whereas meat stays in your GI tract for a long time, it seems possible that carnitine supplements are probably absorbed quickly before the gut bacteria can do their dirty deed, assuming that study is correct.

[meatsauce]

Injectable l-carnitine is the way to. I'll elaborate later.

[YOLF]

Maybe the next advancement in H+ will be a permanent and comfortable IV input on the arm or something.

[solarfingers]

Isn't it probable the TMAO-induced atherosclerosis, like most things, is dose dependent? Were the mice fed proportional doses of carnitine or were they directly given TMAO at some dose, possibly a much higher dose than a human would ever see from eating red meat or even supplementing carnitine? These are some big and obvious questions that should be answered before publishing alarmist articles.

I'm with Luddist on this one. Does anyone know where to read the actual study? Doesn't this go against all of the research on Carnosine up to date? I would like read more about it.

[Kevnzworld]

Isn't it probable the TMAO-induced atherosclerosis, like most things, is dose dependent? Were the mice fed proportional doses of carnitine or were they directly given TMAO at some dose, possibly a much higher dose than a human would ever see from eating red meat or even supplementing carnitine? These are some big and obvious questions that should be answered before publishing alarmist articles.

I'm with Luddist on this one. Does anyone know where to read the actual study? Doesn't this go against all of the research on Carnosine up to date? I would like read more about it.

Carnosine, a dipepeptide also in red meat is a different amino acid.
Red meat is lower in Carnitine , about 100 mg per 4 oz portion than most people supplement. I think the issue is the gut flora. Carnitine taken as a supplement without food is absorbed very quickly in the large intestine. Red meat is difficult to digest. The article mentioned that the bacteria in question comes from red meat, meaning it might not be endogenous to the large intestine. If one doesn't eat red meat, or little of it...and has healthy gut flora , does supplementing ALCAR produce the same amount of TMAO ? Probably not.

[YOLF]

Levels of TMAO in vegan blood are lower if not undetectable. I think that was in the original study or there was commentary regarding this between the scientists.

[niner]

Nat Med. 2013 May;19(5):576-85. doi: 10.1038/nm.3145. Epub 2013 Apr 7.
Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis.
Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL.

1] Department of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. [2] Center for Cardiovascular Diagnostics & Prevention, Cleveland Clinic, Cleveland, Ohio, USA.

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary l-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of l-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma l-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary l-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.

PMID: 23563705

So you probably aren't off the hook if supplementing, instead of getting it from a high-meat diet. The following paper suggests that the conversion of supplemental l-carnitine to TMAO is not a "mouse-only" problem, and happens in humans as well. These particular humans had kidney disease, but that doesn't mean they had particularly abnormal guts.

Curr Drug Metab. 2006 Oct;7(7):811-6.
Oral L-carnitine: metabolite formation and hemodialysis.
Bain MA, Faull R, Milne RW, Evans AM.

Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.

L-Carnitine has important roles in intermediary metabolism and patients with end-stage renal disease who are undergoing hemodialysis may develop a secondary L-carnitine deficiency. The extent of accumulation of the metabolites trimethylamine and trimethylamine-N-oxide when L-carnitine is administered orally has not been investigated previously in this population. Oral L-carnitine at a dose of 1 g daily was administered for twelve days to six patients with end-stage renal disease undergoing hemodialysis thrice weekly. Pre-dialysis plasma concentrations of L-carnitine (mean +/- SD) increased significantly (P < 0.05) from day 1 (baseline; 32.4 +/- 6.1 microM) to day 8 (66.1 +/- 13.8 microM) remaining constant thereafter. Although plasma levels of trimethylamine remained unaltered, the pre-dialysis plasma concentrations of trimethylamine-N-oxide increased significantly (P < 0.05) from day 1 (289.1 +/- 236.1 microM) to day 12 (529.0 +/- 237.9 microM). The hemodialysis clearances for L-carnitine, trimethylamine and trimethylamine-N-oxide were 14.3 +/- 8.2, 14.1 +/- 10.6 and 12.4 +/- 5.4 L/h, respectively, indicating their efficient removal by dialysis. Oral administration of L-carnitine at a dose of 1 g daily increases plasma concentrations of this substance to physiological levels in patients with end-stage renal disease who are undergoing hemodialysis. However, concerns about the possible deleterious consequences of such a dosage regimen still remain given that plasma concentrations of trimethylamine-N-oxide were continually rising and approximately doubled in a two-week period.

PMID: 17073580

My only question is- Would you see the same effect with ALCAR? Like I said above, It's off my list and I don't really miss it.

Edited by niner, 21 June 2013 - 08:26 PM.

[Kevnzworld]

The mechanism seems to be dependent on the ingestion of red meat and the bacteria that it contains or helps foster.
" Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of l-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status "
The OP's study implicated bacteria in red meat, the study quoted mentioned " specific bacterial taxa" but didn't specify which.
I wonder if those of us that don't eat red meat but supplement with ALCAR would have as much concern. I'm sure some TMAO is still produced, but not as much.
I recently had a carotid artery ultra sound completed that showed no thickening. I've been supplementing with 1000 mg of ALCAR and some PP choline for almost ten years, but have not consumed red meat in 20..

[Kevnzworld]

Though just an opinion written by LEF, this is still worth considering for context.
One interesting paragraph mentions the following :
Quote " Heart-healthy salmon is associated with high TMAO levels. Consistency of association is critical in order to draw conclusions from study data across the published literature. The fact that heart-healthy fish consumption is associated with an increase in TMAO levels is challenging to reconcile with the idea that TMAO necessarily causes atherosclerosis. For example, Lloyd et al.52 reported that consumption of salmon, a food known for cardiovascular health benefits, led to an increase in TMAO levels in human test subjects. In another study, it was also observed that TMAO levels increased in individuals consuming large amounts of seafood products.53 ".

The full rebuttal can be found here: http://www.lef.org/f...h&key=Carnitine

[Hebbeh]

Where is everybody getting the idea that the supposed "bad" bacteria is transported within the meat? The study never said that. If you are having "bad" bacteria introduced via the food you are consuming, then you are improperly cooking and preparing your food. It is a well known fact that your gut microbiota is dependent on what you eat due to the fact that different microbes have different nutritional needs just like us. Eating a higher proportion of carbs vs fats vs protein will determine what gut microbes will thrive due to the nutrition that they have available to multiple and thrive on. There are studies that have shown that individuals that live on a lot of "junk" food have different gut microbiota than people eating a healthier diet and studies that show obese individuals have different gut microbiota than healthy people...which studies have implicated "bad" gut microbiota being a contributing cause of obesity...but in reality, is it the chicken or the egg effect (did the "bad" gut microbiota cause obesity or obesity cause the "bad" gut microbiota). Just like you are what you eat, the type of gut microbes are also what they have available to eat...conveniently supplied by your choice of diet. The study simply implicates a diet high in meat as supplying the "food" that allows a gut microbiota that generates TMAO to thrive.

[YOLF]

I stand corrected.

[Luddist]

Where is everybody getting the idea that the supposed "bad" bacteria is transported within the meat? The study never said that. If you are having "bad" bacteria introduced via the food you are consuming, then you are improperly cooking and preparing your food. *snip*

You've never had a medium rare steak? Yum.

[Hebbeh]

Where is everybody getting the idea that the supposed "bad" bacteria is transported within the meat? The study never said that. If you are having "bad" bacteria introduced via the food you are consuming, then you are improperly cooking and preparing your food. *snip*

You've never had a medium rare steak? Yum.

You're missing the point. Your gut microbiota is determined by the nutrition of your diet which also supplies the nutrition for the microbes that are able to colonize your gut. Different microbes thrive under differing conditions and the various microbes that may colonize the gut are determined by the available "food" you supply them. Studies have proven that your diet choices (composition of fats, proteins, carbs, sugars, dairy, etc) will influence the types of microbes that will be able to thrive and flourish on the available food you've supplied via diet. People eating a predominantly high fat vs high carb vs lets say high diary or any other targeted diet (including high junk food) will have vastly different gut microbiota due to the food available (that you've supplied via diet) for the microbes to thrive on. It has nothing to do with a rare steak and any microbes that may or may not be present in the meat. We are not discussing food poisoning via a temporary introduction of e coli or salmonella which is a temporary condition that doesn't represent your gut microbiota over the long haul...only dietary choices determine that by determining the types of microbes that can subsist on those dietary choices.

[JohnD60]

Injectable l-carnitine is the way to. I'll elaborate later.

 

Anyone care to elaborate on benefits of injectable l-carnitine, there seem to numerous sources for it currently on the interweb

[YOLF]

It's a very efficient route of administration and bypasses the gut where it *might* be converted to TMAO (sp?) which would actually put people at risk of atherosclerosis etc.

 

It would also be very handy to keep around in the event that you or someone you know suffers from a heart attack as it can IIRC virtually negate/prevent secondary heart damage when administered immediately after such an occurrence via IV. I remember someone saying that this was actually the only health/longevity thing ALCAR was shown to be good for and that the rest of the reasons for taking it are speculative. It is a good nootropic though but may not be as safe as speculators presume. I haven't read up on ALCAR in a while though. My info could be outdated.

Edited by PerC, 28 December 2014 - 04:23 AM.